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GZMK Gene

protein-coding   GIFtS: 54
GCID: GC05P054320

Granzyme K (Granzyme 3; Tryptase II)

(Previous names: granzyme K (serine protease, granzyme 3; tryptase II))
  See GZMK-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Granzyme K (Granzyme 3; Tryptase II)1 2     granzyme-32
Granzyme K (Serine Protease, Granzyme 3; Tryptase II)1 2     Tryptase II2
NK-Tryp-22 3     EC 3.4.21.-3
NK-tryptase-22 3     Fragmentin-33
TRYP22 3     Granzyme-33
fragmentin-32     EC 3.4.218
Granzyme 32     EC 3.4.21.48
Granzyme K2     

External Ids:    HGNC: 47111   Entrez Gene: 30032   Ensembl: ENSG000001130887   OMIM: 6007845   UniProtKB: P498633   

Export aliases for GZMK gene to outside databases

Previous GC identifers: GC05P054483 GC05P055748 GC05P054290 GC05P054335 GC05P054355 GC05P051293


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for GZMK Gene:
This gene product is a member of a group of related serine proteases from the cytoplasmic granules of cytotoxic
lymphocytes. Cytolytic T lymphocytes (CTL) and natural killer (NK) cells share the remarkable ability to
recognize, bind, and lyse specific target cells. They are thought to protect their host by lysing cells bearing
on their surface 'nonself' antigens, usually peptides or proteins resulting from infection by intracellular
pathogens. The protein described here lacks consensus sequences for N-glycosylation present in other granzymes.
(provided by RefSeq, Jul 2008)

GeneCards Summary for GZMK Gene:
GZMK (granzyme K (granzyme 3; tryptase II)) is a protein-coding gene. Diseases associated with GZMK include arts syndrome, and t-cell large granular lymphocyte leukemia. GO annotations related to this gene include serine-type peptidase activity and serine-type endopeptidase activity. An important paralog of this gene is GZMH.

Gene Wiki entry for GZMK Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000005.9  NC_018916.2  NT_034772.7  
Regulatory elements:
   Regulatory transcription factor binding sites in the GZMK gene promoter:
         Max1   Elk-1   Nkx2-5   NF-kappaB   SRY   POU2F1   POU2F1a   NF-kappaB1   c-Myc   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidGZMK promoter sequence
   Search Chromatin IP Primers for GZMK

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat GZMK


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 5q11.2   Ensembl cytogenetic band:  5q11.2   HGNC cytogenetic band: 5q11.2

GZMK Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
GZMK gene location

GeneLoc information about chromosome 5         GeneLoc Exon Structure

GeneLoc location for GC05P054320:  view genomic region     (about GC identifiers)

Start:
54,320,081 bp from pter      End:
54,330,398 bp from pter
Size:
10,318 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: GRAK_HUMAN, P49863 (See protein sequence)
Recommended Name: Granzyme K precursor  
Size: 264 amino acids; 28882 Da
2 PDB 3D structures from and Proteopedia for GZMK:
1MZA (3D)        1MZD (3D)    
Secondary accessions: B2R563

Explore the universe of human proteins at neXtProt for GZMK: NX_P49863

Explore proteomics data for GZMK at MOPED

Post-translational modifications: 

  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for GZMK (P49863) (see all 6)
     GDSGGPL  CKGDSGG  SGGPLIC  VLTAAHC 


    See GZMK Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_002095.1  
    ENSEMBL proteins: 
     ENSP00000231009  

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    antibodies-online proteins for GZMK (9 products) 

     
    antibodies-online peptides for GZMK

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    4 InterPro protein domains:
     IPR001314 Peptidase_S1A
     IPR001254 Peptidase_S1
     IPR018114 Peptidase_S1_AS
     IPR009003 Trypsin-like_Pept_dom

    Graphical View of Domain Structure for InterPro Entry P49863

    ProtoNet protein and cluster: P49863

    2 Blocks protein domains:
    IPB001254 Serine protease
    IPB001314 Chymotrypsin serine protease family (S1) signature


    UniProtKB/Swiss-Prot: GRAK_HUMAN, P49863
    Similarity: Belongs to the peptidase S1 family. Granzyme subfamily
    Similarity: Contains 1 peptidase S1 domain


    Find genes that share domains with GZMK           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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         Enzyme Numbers (IUBMB): EC 3.4.21.42 EC 3.4.212 EC 3.4.21.-1

         Gene Ontology (GO): 3 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003824catalytic activity ----
    GO:0004252serine-type endopeptidase activity IEA--
    GO:0008236serine-type peptidase activity TAS8656064
         
    Find genes that share ontologies with GZMK           About GenesLikeMe


    Animal Models:
       genOway: Develop your customized and physiologically relevant rodent model for GZMK

    miRNA
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    miRTarBase miRNAs that target GZMK:
    hsa-mir-335-5p (MIRT018327)

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    1 qRT-PCR Assays for microRNA that regulate GZMK:
    hsa-miR-590-3p
    SwitchGear 3'UTR luciferase reporter plasmidGZMK 3' UTR sequence
    Inhib. RNA
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    GRAK_HUMAN, P49863: Secreted. Cytoplasmic granule
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    extracellular5
    chloroplast2
    cytosol1
    lysosome1
    mitochondrion1
    nucleus1

    Gene Ontology (GO): 1 cellular component term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region IEA--

    Find genes that share ontologies with GZMK           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for GZMK About    
    See pathways by source

    SuperPathContained pathways About
    1Granzyme Pathway
    Granzyme Pathway

    1 Downloadable PowerPoint Slide of GeneGlobe Pathway Central Maps for GZMK
        Granzyme Pathway


        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for GZMK
    Interactions:

        GeneGlobe Interaction Network for GZMK

    STRING Interaction Network Preview (showing 2 interactants - click image to see more details)

    Selected Interacting proteins for GZMK (P498633 ENSP000002310094) via UniProtKB, MINT, STRING, and/or I2D (see all 7)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    ENSG00000258947Q135093I2D: score=1 
    TUBB3Q135093I2D: score=1 
    HNRNPKP619783I2D: score=1 
    SETQ011053I2D: score=1 
    SSBP054553I2D: score=1 
    About this table

    Gene Ontology (GO): 1 biological process term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006508proteolysis ----

    Find genes that share ontologies with GZMK           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for GZMK (GRAK)

    3 Novoseek inferred chemical compound relationships for GZMK gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    serine 65.1 9 12384499 (1), 16166056 (1), 8039831 (1), 9569606 (1) (see all 8)
    arginine 17.5 1 1460416 (1)
    oxygen 0 12 18179823 (2)



    Find genes that share compounds with GZMK           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for GZMK gene: 
    NM_002104.2  

    Unigene Cluster for GZMK:

    Granzyme K (granzyme 3; tryptase II)
    Hs.277937  [show with all ESTs]
    Unigene Representative Sequence: BM918927
    2 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000231009(uc003jpl.1) ENST00000512089
    miRNA
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    1 qRT-PCR Assays for microRNA that regulate GZMK:
    hsa-miR-590-3p
    SwitchGear 3'UTR luciferase reporter plasmidGZMK 3' UTR sequence
    Inhib. RNA
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    Additional mRNA sequence: 

    AK312074.1 BC035802.1 U26174.1 U35237.1 

    1 DOTS entry:

    DT.310659 

    24 AceView cDNA sequences:

    U26174 BC035802 AA743283 U35237 AW183169 NM_002104 CD702487 CD687238 
    AA947915 CB987798 BI908502 AU184897 BM918927 BX091409 BI837702 AA970854 
    AA005382 AA699799 AI445141 CB958972 CD705456 CD702028 AA935709 AA004281 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    GZMK expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    GZMK Expression
    About this image


    GZMK expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 2) fully expand
     
     Thymus (Hematopoietic System)
             T-Cytotoxic Cells Thymus
     
     Blood (Cardiovascular System)
             T-Cytotoxic Cells Thymus
    GZMK Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    GZMK Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.277937

    UniProtKB/Swiss-Prot: GRAK_HUMAN, P49863
    Tissue specificity: Expressed in lung, spleen, thymus and peripheral blood leukocytes

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for GZMK gene from Selected species (see all 7)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Gzmk1 , 5 granzyme K1, 5 78.29(n)1
    73.26(a)1
      13 (63.93 cM)5
    149451  NM_008196.11  NP_032222.11 
     1131716085 
    chicken
    (Gallus gallus)
    Aves GZMK6
    granzyme K (granzyme 3; tryptase II)
    42(a)
    1 ↔ 1
    Z(16507933-16514140)
    zebrafish
    (Danio rerio)
    Actinopterygii gzma1 granzyme A 52.12(n)
    42.37(a)
      795070  XM_001335130.2  XP_001335166.1 


    ENSEMBL Gene Tree for GZMK (if available)
    TreeFam Gene Tree for GZMK (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for GZMK gene
    GZMH2  PRTN32  PRSS572  CTSG2  CFD2  ELANE2  CMA12  AZU12  
    GZMM2  GZMA2  GZMB2  
    Selected SIMAP similar genes for GZMK using alignment to 1 protein entry:     GRAK_HUMAN(see all similar genes):
    GZMA    CFD    DF    GZMH    TMPRSS15    KLK9
    CELA1    KLK11    KLK14    KLK8    PLAU    GZMM
    CTRL    CTSG    KLK4    PRSS2    TMPRSS11F    TRY8

    Find genes that share paralogs with GZMK           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for GZMK (see all 278)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 5 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs339346741,2
    C--54318150(+) CCGCC-/CA/CACACACACACACACA/C
    ACACACACACACACACACACACA
    ACACA
    2 -- us2k1 cds10--------
    rs1919077561,2
    --54318268(+) ACTGGA/GATGTA 1 -- us2k10--------
    rs1144893281,2
    C,F--54318287(+) CTGACG/ACCATC 1 -- us2k11Minor allele frequency- A:0.03NA 120
    rs1512846371,2
    --54318291(+) CGCCAC/TCCTGT 1 -- us2k10--------
    rs1841562431,2
    --54318644(+) GTCTAA/GGTCAT 1 -- us2k10--------
    rs1405030421,2
    --54318809(+) ATTAAG/TTTATA 1 -- us2k10--------
    rs355173061,2
    C--54318836(+) TATAGT/GATTAT 1 -- us2k11Minor allele frequency- G:0.00NA 2
    rs64502811,2
    C,F,A--54318844(+) TATTTA/TTTATT 1 -- us2k1 tfbs39Minor allele frequency- T:0.44NA WA CSA EA 369
    rs1859310691,2
    --54318903(+) TCTGCC/TGAGCA 1 -- us2k10--------
    rs731306671,2
    C,F--54319039(+) CTGATG/ACGTGA 1 -- us2k12Minor allele frequency- A:0.09WA 120

    HapMap Linkage Disequilibrium report for GZMK (54320081 - 54330398 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 1 variation for GZMK:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv830301CNV Gain17160897

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing GZMK
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 600784    OMIM disorders: --

    3 diseases for GZMK:    
    About MalaCards
    arts syndrome    t-cell large granular lymphocyte leukemia    allergic asthma

    1 disease from the University of Copenhagen DISEASES database for GZMK:
    Arts syndrome

    Find genes that share disorders with GZMK           About GenesLikeMe

    2 Novoseek inferred disease relationships for GZMK gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    melanoma 13.5 1 16596996 (1)
    tumors 0 1 19201868 (1)


    Export disorders for GZMK gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for GZMK gene, integrated from 10 sources (see all 45):
    (articles sorted by number of sources associating them with GZMK)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Cloning of cDNA for human granzyme 3. (PubMed id 7758581)1, 2, 3, 9 Przetak M.M.... Schmidt B.F. (FEBS Lett. 1995)
    2. The 2.2-A crystal structure of human pro-granzyme K reveals a rigid zymogen with unusual features. (PubMed id 12384499)1, 2, 9 Hink-Schauer C.... Jenne D.E. (J. Biol. Chem. 2002)
    3. Cloning and expression of a second human natural killer cell granule tryptase, HNK-Tryp-2/granzyme 3. (PubMed id 8656064)1, 2, 9 Sayers T.J.... Smyth M.J. (J. Leukoc. Biol. 1996)
    4. Purification of three cytotoxic lymphocyte granule serine proteases that induce apoptosis through distinct substrate and target cell interactions. (PubMed id 1460416)1, 2, 9 Shi L.... Greenberg A.H. (J. Exp. Med. 1992)
    5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S.... Malek J. (Genome Res. 2004)
    6. Characterization of three serine esterases isolated from human IL-2 activated killer cells. (PubMed id 3262682)1, 2 Hameed A.... Podack E.R. (J. Immunol. 1988)
    7. Ignition of p53 bomb sensitizes tumor cells to granzyme K-mediated cytolysis. (PubMed id 19201868)1, 9 Hua G....Fan Z. (J. Immunol. 2009)
    8. Granzyme K directly processes bid to release cytochrome c and endonuclease G leading to mitochondria-dependent cell death. (PubMed id 17308307)1, 9 Zhao T....Fan Z. (J. Biol. Chem. 2007)
    9. Altered levels and molecular forms of granzyme k in plasma from septic patients. (PubMed id 17438453)1, 9 Rucevic M....Lim Y.P. (Shock 2007)
    10. Granzyme K displays highly restricted substrate specificity that only partially overlaps with granzyme A. (PubMed id 19059912)1, 9 Bovenschen N....Kummer J.A. (J. Biol. Chem. 2009)

    (in PubMed, OMIM, and NCBI Bookshelf)
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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 3003 HGNC: 4711 AceView: GZMK Ensembl:ENSG00000113088 euGenes: HUgn3003
    ECgene: GZMK H-InvDB: GZMK

    (According to HUGE)
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    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for GZMK Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
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    Patent Information for GZMK gene:
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    GeneCards and IP:
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